tbuckley/cabot-search huggingface dataset:
Gut microbiota and association with clinical response to anti-PD-1 based immunotherapy combined with chemotherapy in Chinese patients with lung cancer.
Authors: Honghui Zhao, Liyuan He, Li Feng, Zhisong Fan, Long Wang, Jing Han, Xinliang Zhou, Xue Zhang, Dan Li, Jiayin Liu, Feiran Liu, Jing Zuo, Yudong Wang
Journal: Journal of Clinical Oncology (2022)

e21005 Background: The gut microbiome has been demonstrated to be closely related to not only the occurrence of lung cancer but also its anti-PD-1 based immunotherapy and chemotherapy. There is little characteristic analysis of gut microbiota in Chinese lung cancer patients, and the impact of gut microbiota on combined anti-PD-1 treatment and chemotherapy remains unclear. Methods: Fecal samples from 22 healthy volunteers and advanced-NSCLC 21 patients who were treated in the Fourth Hospital of Hebei Medical University from 2019 to 2021 before and after anti-PD-1 treatment combined with chemotherapy were collected. DNA was extracted from all samples, and the V3-V4 region of the bacterial 16S rRNA gene was PCR-amplified using the Illumina sequencing platform. The study results were analyzed using bioinformatic data. Results: The composition of gut microbes in NSCLC patients and healthy people at the phylum level was roughly similar, with Firmicutes as the main phylum. However, there were significant differences in Beta diversity (P&lt;0.05). The bray_curtis principal coordinate analysis revealed a significant difference in the microbiota between patients before and after combined treatment (P&lt;0.05). According to the RECIST 1.1 criteria, the efficacy of the combination therapy was evaluated. The patients with complete remission, partial remission, or stable efficacy after 6 cycles were the clinical benefit response group (CBR, n=10), and the patients with disease progression in the efficacy evaluation were the non-clinical benefit group (NCB, n=8). The results suggested that the CBR group was enriched in Bifidobacterium_longum, Bifidobacterium_adolescentis, Bifidobacterium_bifidum, and Bifidobacterium_breve at the species level (P&lt;0.05) compared with the NCB group. Compared with the median progression-free survival (mPFS) of patients without Bifidobacterium_breve at baseline, the mPFS of patients with the kind of gut bacteria was significantly prolonged (P&lt;0.001).Specifically, mPFS without Bifidobacterium_breve group was 106 days (95% CI: 37-175), mPFS of the Bifidobacterium_breve group was Not Reached (95% CI: NC-NC). Conclusions: The clinical response of combined anti-PD-1 treatment and chemotherapy in advanced NSCLC patients was closely associated with the gut microbiome,and Bifidobacterium_breve may be effective biomarkers to predict the survival benefit of NSCLC combined therapy, which provided new therapeutic targets for modulating the response to cancer therapy.
Clinical assessment of the Omicron outbreak in Europe and trends in morbidity and mortality from COVID-19 and cancer.
Authors: Alessio Cortellini, Juan Aguilar-Company, Rachel Sharkey, Anna Sureda Balari, Alexia Francesca Bertuzzi, Joan Brunet, Gianpiero Rizzo, Marta Perachino, Alvin Jun Xing Lee, Amani Chowdhury, Isabel Ruiz-Camps, Andrea Plaja, Georgina Helen Hanbury, Mieke Van Hemelrijck, Nikolaos Diamantis, Gianluca Gaidano, Federica Grosso, Alessandra Gennari, Josep Tabernero, David J. James Pinato
Journal: Journal of Clinical Oncology (2022)

e18673 Background: Whilst patients (pts) with cancer are at increased risk of adverse outcome from Coronavirus disease 2019 (COVID-19), no evidence exists as to the natural history of the SARS-CoV-2 B.1.1.529 (Omicron) variant in this population. Methods: Capitalizing on OnCovid study data (NCT04393974), a European registry that collects data on consecutive patients with cancer and COVID-19, we analysed COVID-19 morbidity and case fatality rates at 14 days (CFR 14 ) across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: “Pre-vaccination” phase (27/02/2020-30/11/2020), “Alpha-Delta variant” phase (01/12/2020-14/12/2021), “Omicron variant” phase (15/12/2020-31/01/2022). Results: By the data lock of 04/02/2022, 3820 consecutive pts were enrolled, 3473 of whom were eligible for this analysis. Among them, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. Pts diagnosed in the Omicron phase were more likely aged &lt; 65 years (48.6% vs 42.5%, 39.4% p = 0.01), had &lt; 2 comorbidities (61.9% vs 55.6%, 52.1% p = 0.01). They had more advanced-stage tumours (62.1% vs 53.3%, 49.0%, p &lt; 0.01) and were more likely receiving systemic anticancer therapy (SACT) at COVID-19 diagnosis (54.9% vs 43.9%, 39.6%, p &lt; 0.01). Proportions of fully vaccinated/boosted pts were higher in the Omicron phase (33.9%-48.1%) compared to the Alpha-Delta phase (16.6%-2.3%, p &lt; 0.01). Pts diagnosed in the Omicron phase had improved CFR 14 (9.0% vs 13.9%, 23.1%, p &lt; 0.01) lower hospitalization rates due to COVID-19 (24.4% vs 41.4%, 56.6%, p &lt; 0.01), lower complications rates (15.3% vs 33.6%, 39.4%, p &lt; 0.01) and reduced need for COVID-19 specific therapy (22.4% vs 43.0%, 65.7% p &lt; 0.01) compared to the Alpha-Delta and pre-vaccinal phase. After adjusting for country of origin, sex, age, comorbidities, tumour stage, status and receipt of SACT at COVID-19, patients diagnosed in the Omicron phase displayed the lowest risk of death at 14 days compared to earlier phases. Similarly, rates of hospitalization and complicated COVID-19 were lowest for Omicron phase. Conclusions: This is the first study to portray the evolution of the SARS-CoV-2 Omicron outbreak in Europe, documenting an improvement in all COVID-19 outcomes compared to earlier phases of the pandemic. Enhanced healthcare capacity, improved disease management, immunization campaigns alongside differential virulence of viral strains are likely contributing to improved outcomes across phases.[Table: see text]
Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study
Authors: Max A. Seibold, Camille M. Moore, Jamie L. Everman, Blake J.M. Williams, James D. Nolin, Ana Fairbanks-Mahnke, Elizabeth G. Plender, Bhavika B. Patel, Samuel J. Arbes, Leonard B. Bacharier, Casper G. Bendixsen, Agustin Calatroni, Carlos A. Camargo, William D. Dupont, Glenn T. Furuta, Tebeb Gebretsadik, Rebecca S. Gruchalla, Ruchi S. Gupta, Gurjit K. Khurana Hershey, Liza Bronner Murrison, Daniel J. Jackson, Christine C. Johnson, Meyer Kattan, Andrew H. Liu, Stephanie J. Lussier, George T. O’Connor, Katherine Rivera-Spoljaric, Wanda Phipatanakul, Marc E. Rothenberg, Christine M. Seroogy, Stephen J. Teach, Edward M. Zoratti, Alkis Togias, Patricia C. Fulkerson, Tina V. Hartert
Journal: Journal of Allergy and Clinical Immunology (2022)
Prognostic risk factors of grade and stage migration in patients under active surveillance: A prospective cohort study from Bladder cancer Italian Active Surveillance register (BIAS)
Authors: N. Frego, R. Contieri, D. Maffei, V. Fasulo, A. Uleri, E. Beatrici, P. Diana, M. Lazzeri, A. Saita, G. Lughezzani, N.M. Buffi, P. Casale, R. Hurle
Journal: European Urology (2022)
A novel focal therapy for patients with localized prostate cancer: Targeted Microwave Ablation (TMA) under Organ-Based Tracking Fusion® (OBT) – preliminary results of an ablate-and-resect study (FOSTINE 01b)
Authors: A. Peltier, G. Assenmacher, R. Diamand, E. Hawaux, K. Limani, N. Sirtaine, M. Ben Aziz, Y. Lefebvre, M. Lemort, R. Van Velthoven
Journal: European Urology (2022)
Systematic investigation of immune-related lncRNA landscape reveals a potential long non-coding RNA signature for predicting prognosis in kidney renal clear cell carcinoma.
Authors: Kepu Liu, Zhibin Li, Dongli Ruan, Huilong Wang, Wei Wang, Geng Zhang
Journal: Journal of Clinical Oncology (2022)

e16510 Background: Increasing evidence has revealed that long non-coding RNAs (lncRNAs) play a crucial role in cancer immunity. However, the comprehensive landscape of immune infiltration-associated lncRNAs and their potential roles in the prognosis and diagnosis of kidney renal clear cell carcinoma (KIRC) remains largely unexplored. Methods: The transcriptomics data, expression profiles, and clinical information of KIRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. Novel lncRNAs were identified by a custom pipeline. The infiltration of immune cells was calculated by ssGSEA. K-means consensus method was used to cluster KIRC samples in different groups. Immune-related lncRNAs were obtained by differential expression analysis based on these groups. Univariate Cox regression, LASSO regression, and multivariate Cox regression analysis were performed on GEO datasets to construct an immune-related lncRNAs signature for predicting the prognosis of KIRC. And then, validated the prognostic signature in TCGA data. Results: Based on 261 samples from KIRC patients, tens of thousands of novel lncRNA genes were identified. KIRC samples were clustered into three immune clusters based on the infiltration of immune cells. Based on these groups, 241 immune-related lncRNAs were obtained. Moreover, a large part of immune-related lncRNAs could be detected in urinary samples of KIRC. Through a series of analyses, three immune-related lncRNAs were identified as a prognostic signature for KIRC. KIRC patients in the high-risk group had a shorter OS than those in the low-risk group both in the training set (P &lt; 0.001) and TCGA data (P &lt; 0.001), respectively. The AUC was 0.9 in the training set. Univariate and multivariate Cox regression analysis confirmed that the immune-related lncRNAs signature could be an independent prognostic factor both in the training set and TCGA data. Conclusions: All these findings provide a more comprehensive lncRNAs catalog for investigating the lncRNAs and provide a novel approach for the effective prediction of clinical outcomes in KIRC.
Long-term survival in newly-diagnosed ovarian cancer patients.
Authors: Elizabeth A. Szamreta, Yeran Li, Matthew J. Monberg, Megan Othus
Journal: Journal of Clinical Oncology (2022)

e17543 Background: A proportion of women with ovarian cancer, even those with advanced-stage disease, will experience long-term survival post diagnosis. Mixture cure modeling provides insight into factors related to both short-term recurrence and death as well as long-term survival. The goals of this study were to estimate the long-term survival rate, and to evaluate associations between patient characteristics and the long-term survival rate and landmark 5- and 10- year survival, in a sample of newly-diagnosed ovarian cancer patients. Methods: The Tempus EMR dataset contains patients from academic &amp; community oncology centers in the U.S. This study included adult women with a new primary diagnosis of ovarian, fallopian tube, or peritoneal cancer between 2000 and 2020. Women treated with a poly-ADP ribose polymerase inhibitor (PARPi), pembrolizumab, or nivolumab were excluded (n = 947; final sample size = 6,598). Mixture cure models were used to estimate the long-term survival rate (probability of living as long as an age- and gender-matched person without ovarian cancer), overall and stratified by patient demographic &amp; clinical characteristics. Relative importance of variables associated with long-term survival was evaluated using logistic regression models with 5- and 10-year landmark outcomes. Results: Younger age, earlier stage, lower grade, favorable ECOG score, and platinum sensitivity were associated with better overall survival (OS). The long-term survival rate in our model was 25.0% (95% CI: 21.5-28.9). The long-term survival rate was higher for age &lt; 65 vs. age 75+ [29.0% (24.8-33.6) vs. 10.5% (2.9-31.6)], early vs. advanced stage disease [62.0% (41.4-78.9) vs. 17.8% (14.1-22.2)], grade 1-2 vs. 3-4 [31.4% (12.1-60.3) vs. 20.4% (14.6-27.8)], ECOG 0-2 vs. 3-4 [26.1% (21.4-31.3) vs. 2.6% (0.05- 56.5)], and platinum sensitive vs. platinum resistant patients [47.5% (43.1-51.9) vs. 9.4% (7.0-12.5)]. Analyzing 5- and 10-year landmarks [n = 3,944 (59.8%), n = 3,107 (47.1%), respectively] in multivariable logistic regression models, platinum sensitivity had the strongest association, followed by cancer stage. Conclusions: Understanding differences in long-term survival based on patient characteristics is important for clinical decision-making and personalizing treatment. Overall, one quarter of ovarian cancer patients were long-term survivors; long-term survivors were more likely to be younger and have earlier stage disease, low grade disease, better performance status, or sensitivity to platinum-based therapy. These results also provide a baseline to evaluate long-term survival in patients on newer therapies such as PARPi when sufficient follow-up data are available.
Analysis of MET genetic aberrations in Chinese solid tumor patients.
Authors: Guanglong Huang, Zhengying Bian, Juan Ma, Siqi Chen, Guanghua Lu, Ran Ding, Fanfeng Bu
Journal: Journal of Clinical Oncology (2022)

e15031 Background: Mesenchymal-epithelial transition (MET) gene encodes a member of the receptor tyrosine kinase family of proteins and is a proto-oncogene. MET gene takes part in various signaling pathways such as PI3K/AKT, Ras/MAPK, and JAK/STAT which are associated with tumor development and progression. This study aimed to reveal MET aberrated characteristics in Chinese solid tumor patients and explore the occurrence of MET oncogenic variants in solid tumors. Methods: This study retrospectively analyzed MET alterations in 1856 solid tumor patients in China from laboratory of Simcere Diagnosis (Nanjing, China) during 2019-2021. Next-generation sequencing (NGS) was performed to detect gene mutations in tumor or blood samples of the patients. Results: We screened out 1856 patients with MET gene alterations from 45717 patients with solid tumor. The high frequency of MET gene alterations was lung cancer (72.8%), colorectal cancer (10.7%), gastric cancer (4.9%), and liver cancer (2.7%). MET gene variants included missense (61.7%), copy number variation (copy number≥5) (15.4%), truncation (7.9%), splicing site variant (7.2%),fusion (1.7%),and in-frame insertion/deletions (0.9%). Among them, MET amplification was detected in 285 patients, and 93 patients carried high-level MET amplification (copy number≥10). High-level MET amplification was most frequently detected in lung cancer (41, 44.1%), gastric cancer (17, 18.3%) and liver cancer (14, 15.1%). MET exon 14 skipping was detected in 287 solid tumor patients (15.5%), of which 277 patients were lung cancer, the remaining were liver cancer, colorectal cancer, gastric cancer, osteosarcoma, melanoma, bladder cancer and glioma. We analyzed MET exon 14 alterations and classified them into 4 subgroups according to the alteration types and locations. The most common alterations were at splice donor sites (215, 74.91%), followed by the splice acceptor sites (35, 12.20%), Y1003 site (5, 1.74%), and other types (32, 11.15%). Other types included insertion or deletion in MET intron 13 or 14, for example, c.3028+21_3028+65del, c.2888-20_2888-11del, c.2888-27_2888-9del, etc. 7 lung cancer patients carried MET exon 14 skipping and MET amplification simultaneously. 36 patients carried MET gene fusions, and mostly were lung cancer (22, 61.1%). The breakpoints often located in exon 2 of MET (4, 11.1%). Conclusions: We discovered MET alterations in multiple types of solid tumors in this study. We found classic MET exon 14 skipping and MET high-level amplification in solid tumors except for lung cancer. It suggested that the activation of MET-driven signaling pathway was ubiquitous in pan-cancer, which might benefit from MET inhibitors.
Analysis of Electrophysiological Activation of the Uterus During Human Labor Contractions
Authors: Alison G. Cahill, Zichao Wen, Hui Wang, Peinan Zhao, Zhexian Sun, Alan L. Schwartz, Yong Wang
Journal: JAMA Network Open (2022)

electrical activities can be reliably and cost-effectively measured using bioelectrodes in clinical environments, which enable EMMI to "see" and quantify the uterine contractions in 3-D noninvasively for each patient during labor. 6This electrophysiological difference underlying uterine contractions may indicate the existence of myometrial memory, leading to more rapid labor progression of multiparous patients than nulliparous patients.In the short term, EMMI may facilitate translational studies aimed at defining the mechanisms underlying normal human labor.The major limitations of this study are the cost and accessibility of EMMI and the small patient cohort.We are developing a low-cost, portable, bedside EMMI system that does not rely on magnetic resonance imaging and can be applied to a larger patient cohort in clinical trials aimed at testing interventions to estimate when women experiencing contractions will deliver, how long labor will take, or which women will require intervention to prevent labor arrest, preterm birth, and postpartum hemorrhage.
Trend of sphincter-preserving surgeries for resectable low rectal cancer: A 20-year experience in China.
Authors: Qingqing HU, Kuo Zheng, Yuting Yao, Yuan Zhou, Ronggui Meng, Hao Wang, Liqiang Hao, Yongjing Zhang, Hong Qiu, Wei Zhang
Journal: Journal of Clinical Oncology (2022)

3615 Background: Over the last decades, patients with low rectal cancer have realized better functional, morbidity, and quality-of-life outcomes from improvements in surgical techniques in sphincter preservation. We aimed to quantify the trend in sphincter-preserving surgeries for low rectal cancer over 20 years in China. Methods: Between November 1999 and October 2021, a cohort of patients with pathologically confirmed primary malignant rectal tumor ≤5cm from the anal verge and who received selective surgery at Changhai Hospital, was identified. Demographic and clinical data were extracted from electronic medical records. Survival data were collected from outpatient medical records and follow-up phone interviews. A Joinpoint Regression Model was used to analyze trends in surgical procedures by average annual percentage change (AAPC). A Cox proportional hazards regression model adjusting for demographic and clinicopathological confounders was used to assess the overall survival for patients with sphincter-preserving surgery vs. abdominoperineal resection (APR). Results: Among 19,276 patients with colorectal cancer, 4,072 (21.1%) had a tumor in the low rectum during the study period; 3,025 (74.2%) underwent a sphincter-preserving surgery and 1,047 (25.7%) received APR. Sphincter-preserving surgery increased 3.6% per year (AAPC 3.6, p=.006). Anterior resection was the most performed procedure (86.3%) and maintained a steady trend (AAPC 0.13, p=.49), while intersphincteric resection (including conformal sphincter preservation operation) increased 49.4% annually (AAPC 49.4, p=.003). Laparoscopic techniques increased 15.1% per year (AAPC 15.1, p=.035). Sphincter-preserving surgery increased annually for tumors ≤2cm, 2-3cm and 3-4cm from the anal verge (AAPC 7.08, p=.001; 4.69, p=.001; 2.66, p=.001, respectively). A total of 2,854 patients had sufficient vital status data for inclusion in the survival analysis. The characteristics of those with and without a follow-up encounter were comparable. Patients with sphincter-preserving surgery had a lower risk of death compared to APR (adjusted HR 0.78, 95% CI, 0.65-0.93, p=.01). Conclusions: Utilization of sphincter-preserving surgeries increased significantly over the last 20 years. Patients with low rectal cancer who underwent sphincter preservation had better survival than similar patients who underwent APR.[Table: see text]
Phase II study of nivolumab (nivo) with relatlimab (rela) in patients (pts) with first-line advanced melanoma: Early on-treatment major pathologic response on biopsy.
Authors: Lilit Karapetyan, Arivarasan Karunamurthy, Anthony Cillo, Anjali Rohatgi, Ryan Campbell Massa, William E. Gooding, Yana G. Najjar, Diwakar Davar, Jason J. Luke, Tullia C. Bruno, Dario Vignali, John M. Kirkwood
Journal: Journal of Clinical Oncology (2022)

9514 Background: A phase II study of nivo and rela was designed to evaluate the antitumor activity and mechanism of this combination and components for first-line treatment of pts with advanced melanoma. Pts received lead-in treatment with 1 cycle of nivo (480mg IV q4wk), rela (160mg IV q4wk), or nivo-rela followed by combination therapy. We assessed the effect of each lead-in treatment on immune-related pathological response (irPR) at 4-wk biopsy to develop early biomarkers of antitumor response. Methods: Core biopsy of an index lesion was performed at baseline and after 4 wk on-treatment. Immune characteristics of pathological response were assessed on H&amp;E sections, including presence of tumor-infiltrating lymphocytes (TIL), neovascularization, proliferative fibrosis, plasma cells, and lymphoid aggregates. irPR score was calculated as described by Stein JE et al Ann Oncol 2019, from 0 (no irPR features) to 3 (major pathologic response on biopsy [MPRbx], ≤10% residual viable tumor). We assessed the association between irPR and radiological response (RECIST v1.1) at 4-wk evaluations. Results: The current cohort includes 22 pts, median age = 67, male = 13. Pts were randomized to nivo = 7, rela = 7, and nivo-rela = 8 lead-in groups. Two pts had no irPR evaluation due to early progression and unscorable tumor. Among 20 evaluable pts, proliferative fibrosis, neovascularization, plasma cells, brisk TIL, and lymphoid aggregates were identified in 50%, 35%, 26.3%, 25%, and 5% of cases, respectively. Lead-in nivo (n = 2/6), rela (n = 0/6), and nivo-rela (n = 3/8) resulted in irPR = 3 in 25% of pts. Radiological response was identified as partial response (PR) = 1/22 (4.5%), stable disease (SD) = 12/22 (54.5%), and progressive disease (PD) = 9/22 (41%). Among pts with PD, 44% received rela-, 33% nivo-, and 22% nivo-rela- lead-in. Pts with irPR score = 3 had radiological PR = 1, SD = 3, and PD = 1 at 4wks. No association was found between MPRbx and radiological response at 4 wks. Conclusions: Four-wk MPRbx may serve as an early biomarker of treatment response in advanced melanoma. Lead-in treatment resulted in MPRbx of 25% and was greatest with nivo-rela lead-in. Correlations between 4 wk MPRbx and later radiological responses, survival and other endpoints will be made at completion of trial accrual. Clinical trial information: NCT03743766. [Table: see text]